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About

Li-Huei Tsai received her Ph.D degree from the University of Texas Southwestern Medical Center at Dallas. Dr. Tsai completed her postdoctoral work at Cold Spring Harbor laboratory and Massachusetts General Hospital. In 1994, Dr. Tsai joined the faculty in the Department of Pathology at Harvard Medical School and was named an investigator of Howard Hughes Medical Institute in 1997. In 2006, she was appointed Professor in the Department of Brain and Cognitive Sciences, and joined the Picower Institute for Learning and Memory at MIT. Since 2009, Dr. Tsai has served as the Director of the Picower Institute for Learning and Memory.

Research

Our primary goal is to elucidate the pathological mechanisms underlying neurological disorders affecting learning & memory. The major research areas include brain aging and Alzheimer’s disease.

For more than a decade, in exploring possible mechanisms underlying Alzheimer’s disease, Dr. Tsai has focused on a protein kinase called Cdk5. It’s crucial to the process by which new neurons form and migrate to the outside cortical layers during development; at the same time, there’s emerging evidence that it’s key to the neuronal plasticity that allows us to remember and learn. Research in the Tsai lab suggests, for example, that briefly exposing neurons to a certain protein associated with Cdk5 boosts synaptic growth and improves certain kinds of memory; extended exposure to the same protein triggers loss of neurons and severe cognitive decline.

In addition, Dr. Tsai has both accelerated the work of her own lab and advanced the field as a whole by developing an innovative mouse model that can be induced to experience the profound neurodegeneration of Alzheimer’s, and that develops full-blown symptoms in a month or two, rather than a year or more. This adaptable mouse model is ideal for Dr. Tsai’s current work – the understanding of disease mechanisms and the search for new approaches to therapeutic intervention of neurodegeneration. Recently, her group used an unbiased systems biology approach to conduct and compare transcriptomic and epigenomic profiles of the p25 mice at pre- and symptomatic stages to the data of postmortem human AD brains. Through this approach, her group discovered that the gene expression changes are remarkably similar between the mouse and human pathologies and that neuronal plasticity genes are decreased, while innate immune response genes are strikingly increased. They also investigated whether human AD GWAS risk alleles were enriched in these profiles and found that the non-coding enhancer regions actually encode the risk, not the genes themselves, and that these are significantly enriched in the increased immune response genes. Together, these results suggest a remarkably new perspective on the disease. Namely, that genetic risk for AD influences the disease specifically through immune response genes.

Her lab currently employs induced pluripotent stem cells and genome editing techniques to model AD, and uses in vivo recordings, brain circuit tracing, large scale imaging and optogenetics to gain further insight into the pathophysiology of AD.